Cyclohexene regioselective alkylation

Progress has been made toward enantioselective and highly regioselective Michael type alkylations of 2-cyclohexen-l -one using alkylcuprates with chiral auxiliary ligands, e. g., anions of either enantiomer of N-[2-(dimethylamino)ethyl]ephedrine (E. J. Corey, 1986), of (S)-2-(methoxymethyl)pyrrolidine (from L-proline R. K. EHeter, 1987) or of chiramt (= (R,R)-N-(l-phenylethyl)-7-[(l-phenylethyl)iinino]-l,3,5-cycloheptatrien-l-amine, a chiral aminotro-ponimine G. M. Villacorta, 1988). Enantioselectivities of up to 95% have been reported. 

Alkyl-substituted phenols and alkanes were also oxidized to give the corresponding oxygenated products. In the case of isophorene, 3-formyl-5,5-dimethyl-2-cyclohexen-l-one was obtained selectively [110], The regioselectivity of the oxidation was remarkably different from that observed with the corresponding homogeneous analog, which produced 1,4-diketone as a major product [110] ... 

This procedure for stereoselective 1,4-functionalization of 1,3-dienes is based on 1,4-acetoxychlorination,2 and allows the preparation of 1,4-disubstituted 2 cyclohexenes with full stereocontrol of the carbon-carbon bond formation in the 4-position. It is also highly regioselective. Other procedures3 4 for obtaining 4-alkyl-substituted 3-cyclohexenol derivatives use 1,3-cyclohexadiene monoepoxide as starting material. None of the previous methods allow the selective preparation of both stereoisomers as shown here. 

All the polymers of Table III have been applied for the epoxidation of olefins with alkyl hydroperoxides. For example, the polymers with iminodiacetic acid or diethylene triamine groups were used for the regioselective epoxidation of (E)-geraniol with t-BuOOH to the 2,3-epoxide (225), whereas the Mo anchored to the diphenylphosphinopolystyrene catalyst is used in the epoxidation of cyclohexene with t-BuOOH (228). The polymer-supported molybdenyl thioglycolate has also been used for the catalytic oxidation of thiols and phosphines with air or pyridine N-oxide as the oxidant (234). 

Alkylation of allylic alcohols. The alkylation of allylic alcohols by Grignard reagents in the presence of nickel-phosphine1-2 catalysts has been shown to be rtereospecific in the case of the cis- and ms-4-methyl-2-cyclohexene-l-ols (2)J. The hydroxyl group is replaced with inversion, but the regioselectivity is different. In... 

Another route to alkenyl radicals is by addition of radicals to alkynes. An application of this procedure, which serves as a model for the synthesis of the CD ring system of cardiac aglycones was reported by Stork and co-workers (4.55). The initial alkyl radical, formed selectively from the bromide 61 attacks the alkyne regioselectively to give an intermediate alkenyl radical, which reacts further with the alkene of the cyclohexene to give the product 62. A mixture of alkene stereoisomers is produced owing to the ease of E-Z alkenyl radical isomerization. 

The catalyst can be recovered and reused. The reaction is completed in a few minutes at room temperature. Sonication does not change the regioselectivity, e.g., with toluene. Similarly, alkylation of benzene with cyclohexene in the presence of aluminum chloride on silica undergoes a sonochemical acceleration of ca. 10 times, essentially due to the improved mass transport induced by sonication.162 jhg formylation of polystyrene represents an interesting case of a triphasic system, constituted by the polymer, aluminum chloride, and dichloromethyl methylether. Sonication provides a significant improvement. 

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